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KMID : 0603520020070010027
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Journal of Korean Association of Cancer Prevention
2002 Volume.7 No. 1 p.27 ~ p.33
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Regulation of Transcriptional Activity of Insulin-like Growth Factor II (IGF-II)
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Bae Myung-Ho
Song Hyun-Seok
Bae Soo-Kyung
Lee Seok-Ki
Lee Sae-Won
Kim Chul-Woo
Kim Kyu-Won
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Abstract
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It has been known that IGF-II is required for normal pre-natal growth of the liver in rodents and humans and has an angiogenic effect in experimental animals. The human IGF-II gene is a complex transcription unit containing four different promoters, leading to the formation of multiple IGF-II mRNA. The four promoters can be activated in a development-dependent and tissue-dependent manner. The human IGF-II promoter P3 is used in many fetal tissues and is highly active in several tumors, suggesting autocrine effects of IGF-II in tumor progression. In this study, we confirmed increased transcriptional activity of IGF-II P3 promoter under hypoxia. In addition, we showed that MAPK pathway is not involved in activation mechanism of IGF-II P3 promoter by using MAPK nhibitors and JNK dominant negative mutants. Moreover, we investigated the effect of hypoxia on the transcriptional activity of Egr-l, possible transcription factor regu1ating IGF-II. These results may examine the molecular signaling mechanism of carcinogenesis and metastasis in hepatocellular carcinoma and can apply to the development of cancer diagnosis and therapy.
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KEYWORD
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Insulin like Growth Factor-I, , Mitogen activated protein kinase, Transcriptional activity, Hypoxia
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